19,027 results match your criteria complex modifications

Phage-encoded ten-eleven translocation dioxygenase (TET) is active in C5-cytosine hypermodification in DNA.

Proc Natl Acad Sci U S A 2021 Jun;118(26)

Research Department, Molecular Enzymology Division, New England Biolabs, Ipswich, MA 01938

TET/JBP (ten-eleven translocation/base J binding protein) enzymes are iron(II)- and 2-oxo-glutarate-dependent dioxygenases that are found in all kingdoms of life and oxidize 5-methylpyrimidines on the polynucleotide level. Despite their prevalence, few examples have been biochemically characterized. Among those studied are the metazoan TET enzymes that oxidize 5-methylcytosine in DNA to hydroxy, formyl, and carboxy forms and the euglenozoa JBP dioxygenases that oxidize thymine in the first step of base J biosynthesis. Read More

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Two-Dimensional Mass Spectrometry Analysis of IgG1 Antibodies.

J Am Soc Mass Spectrom 2021 Jun 21. Epub 2021 Jun 21.

Department of Chemistry, University of Warwick, Coventry CV4 7AL, United Kingdom.

Two-dimensional mass spectrometry (2DMS) is a new, and theoretically ideal, data-independent analysis tool, which allows the characterization of a complex mixture and was used in the bottom-up analysis of IgG1 for the identification of post-translational modifications. The new peak picking algorithm allows the distinction between chimeric peaks in proteomics. In this application, the processing of 2DMS data correlates fragments to their corresponding precursors, with fragments from precursors which are <0. Read More

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Chemoenzymatic Total Synthesis of GM3 Gangliosides Containing Different Sialic Acid Forms and Various Fatty Acyl Chains.

J Org Chem 2021 Jun 21. Epub 2021 Jun 21.

Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, United States.

Gangliosides are sialic acid-containing glycosphingolipids that have been found in the cell membranes of all vertebrates. Their important biological functions are contributed by both the glycan and the ceramide lipid components. GM3 is a major ganglioside and a precursor for many other more complex gangliosides. Read More

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Graphene Array-Based Anti-fouling Solar Vapour Gap Membrane Distillation with High Energy Efficiency.

Nanomicro Lett 2019 Jun 10;11(1):51. Epub 2019 Jun 10.

Joint CSIRO-QUT Sustainable Processes and Devices Laboratory, P.O. Box 218, Lindfield, NSW, 2070, Australia.

Photothermal membrane distillation (MD) is a promising technology for desalination and water purification. However, solar-thermal conversion suffers from low energy efficiency (a typical solar-water efficiency of ~ 50%), while complex modifications are needed to reduce membrane fouling. Here, we demonstrate a new concept of solar vapour gap membrane distillation (SVGMD) synergistically combining self-guided water transport, localized heating, and separation of membrane from feed solution. Read More

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Disruptions in maternal and child health service utilization during COVID-19: analysis from eight sub-Saharan African countries.

Health Policy Plan 2021 Jun 19. Epub 2021 Jun 19.

Development Research Group, The World Bank, 1818 H St NW, Washington, DC 20433, USA.

The coronavirus-19 pandemic and its secondary effects threaten the continuity of essential health services delivery, which may lead to worsened population health and a protracted public health crisis. We quantify such disruptions, focusing on maternal and child health, in eight sub-Saharan countries. Service volumes are extracted from administrative systems for 63 954 facilities in eight countries: Cameroon, Democratic Republic of Congo, Liberia, Malawi, Mali, Nigeria, Sierra Leone and Somalia. Read More

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A novel CAD/CAM composite occlusal splint for intraoperative verification in single-splint two-jaw orthognathic surgery.

Biomed J 2021 Jun 15. Epub 2021 Jun 15.

Craniofacial Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address:

Background: Previous computer-generated splints were designed and produced without modification than the traditional occlusal splints, which did not facilitate surgeon's intraoperative judgment in the single-splint two-jaw orthognathic surgery. Modifications of the digital occlusal splint can be achieved using computer-aided design and computer-aided manufacturing (CAD/CAM) software. This study reported the design, clinical application and validation of a novel CAD/CAM occlusal splint. Read More

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Platelet-derived growth factor receptor beta activates Abl2 via direct binding and phosphorylation.

J Biol Chem 2021 Jun 15:100883. Epub 2021 Jun 15.

Departments of Molecular Biophysics and Biochemistry Yale University, New Haven, Connecticut 06510; Departments of Neuroscience Yale University, New Haven, Connecticut 06510. Electronic address:

Abl family kinases are nonreceptor tyrosine kinases activated by diverse cellular stimuli that regulate cytoskeleton organization, morphogenesis, and adhesion. The catalytic activity of Abl family kinases is tightly regulated in cells by a complex set of intra- and intermolecular interactions and post-translational modifications. For example, the platelet-derived growth factor receptor beta (PDGFRβ), important for cell proliferation and chemotaxis, is a potent activator of Abl family kinases. Read More

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Cell cycle regulation by complex nanomachines.

FEBS J 2021 Jun 18. Epub 2021 Jun 18.

Institute of Cancer Research, London, UK.

The cell cycle is the essential biological process where one cell replicates its genome and segregates the resulting two copies into the daughter cells during mitosis. Several aspects of this process have fascinated humans since the nineteenth century. Today the cell cycle is exhaustively investigated because of its profound connections with human diseases and cancer. Read More

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Epigenetics Identifier screens reveal regulators of chromatin acylation and limited specificity of acylation antibodies.

Sci Rep 2021 Jun 17;11(1):12795. Epub 2021 Jun 17.

Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC, Leiden, The Netherlands.

The collection of known posttranslational modifications (PTMs) has expanded rapidly with the identification of various non-acetyl histone lysine acylations, such as crotonylation, succinylation and butyrylation, yet their regulation is still not fully understood. Through an unbiased chromatin immunoprecipitation (ChIP)-based approach called Epigenetics-IDentifier (Epi-ID), we aimed to identify regulators of crotonylation, succinylation and butyrylation in thousands of yeast mutants simultaneously. However, highly correlative results led us to further investigate the specificity of the pan-K-acyl antibodies used in our Epi-ID studies. Read More

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Comprehensive glycoproteomics shines new light on the complexity and extent of glycosylation in archaea.

PLoS Biol 2021 Jun 17;19(6):e3001277. Epub 2021 Jun 17.

Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Glycosylation is one of the most complex posttranslational protein modifications. Its importance has been established not only for eukaryotes but also for a variety of prokaryotic cellular processes, such as biofilm formation, motility, and mating. However, comprehensive glycoproteomic analyses are largely missing in prokaryotes. Read More

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Bromodomain and extraterminal (BET) protein inhibition of IgG/IgE production in murine B cells is counter-balanced by a strong Th2 bias.

Clin Transl Immunology 2021 30;10(6):e1280. Epub 2021 May 30.

Control of the B cell Response & Lymphoproliferation CNRS UMR 7276 INSERM U1262 Limoges University Limoges France.

Objectives: Inhibitors of bromodomain and extra terminal domain (BET) proteins are a new and growing class of anti-cancer drugs, which decrease oncogene expression by targeting superenhancers. Antibody production is another physiological process relying on superenhancers, and it remains to be clarified whether potential immunomodulatory properties of BET inhibitors might impact humoral immunity and allergy.

Methods: We thus evaluated humoral immune responses and their Th2 context and in mice following treatment with the classical BET-inhibitor JQ1. Read More

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Non-alcoholic fatty liver disease - how to effectively fight the nowadays most common liver disease?

Václav Šmíd

Cas Lek Cesk 2021 ;160(2-3):65-70

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease nowadays. It is referred to as liver manifestation of metabolic syndrome. Given the growing incidence of diabetes and obesity, we can confidently say that we will be, or even are facing, a NAFLD pandemic in the near future. Read More

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Enhanced single-node lattice Boltzmann boundary condition for fluid flows.

Phys Rev E 2021 May;103(5-1):053308

Department of Computer Science, University of Geneva, 1204 Geneva, Switzerland.

We propose a procedure to implement Dirichlet velocity boundary conditions for complex shapes that use data from a single node only, in the context of the lattice Boltzmann method. Two ideas are at the base of this approach. The first is to generalize the geometrical description of boundary conditions combining bounce-back rule with interpolations. Read More

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Conformational control of PdL assemblies with unsymmetrical ligands.

Chem Sci 2019 Nov 28;11(3):677-683. Epub 2019 Nov 28.

Department of Chemistry, Imperial College London, Molecular Sciences Research Hub 80 Wood Lane London W12 0BZ UK

With increasing interest in the potential utility of metallo-supramolecular architectures for applications as diverse as catalysis and drug delivery, the ability to develop more complex assemblies is keenly sought after. Despite this, symmetrical ligands have been utilised almost exclusively to simplify the self-assembly process as without a significant driving foa mixture of isomeric products will be obtained. Although a small number of unsymmetrical ligands have been shown to serendipitously form well-defined metallo-supramolecular assemblies, a more systematic study could provide generally applicable information to assist in the design of lower symmetry architectures. Read More

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November 2019

Designing naphthopyran mechanophores with tunable mechanochromic behavior.

Chem Sci 2020 Apr 17;11(17):4525-4530. Epub 2020 Apr 17.

Division of Chemistry and Chemical Engineering, California Institute of Technology Pasadena California 91125 USA

Mechanochromic molecular force probes conveniently report on stress and strain in polymeric materials through straightforward visual cues. We capitalize on the versatility of the naphthopyran framework to design a series of mechanochromic mechanophores that exhibit highly tunable color and fading kinetics after mechanochemical activation. Structurally diverse naphthopyran crosslinkers are synthesized and covalently incorporated into silicone elastomers, where the mechanochemical ring-opening reactions are achieved under tension to generate the merocyanine dyes. Read More

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RNA-directed DNA methylation prevents rapid and heritable reversal of transposon silencing under heat stress in Zea mays.

PLoS Genet 2021 Jun 14;17(6):e1009326. Epub 2021 Jun 14.

Department of Botany and Plant Pathology, Purdue University, West Lafayette, Indiana, United States of America.

In large complex plant genomes, RNA-directed DNA methylation (RdDM) ensures that epigenetic silencing is maintained at the boundary between genes and flanking transposable elements. In maize, RdDM is dependent on Mediator of Paramutation 1 (Mop1), a putative RNA dependent RNA polymerase. Here we show that although RdDM is essential for the maintenance of DNA methylation of a silenced MuDR transposon in maize, a loss of that methylation does not result in a restoration of activity. Read More

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Neuromorphic Time-Multiplexed Reservoir Computing With On-the-Fly Weight Generation for Edge Devices.

IEEE Trans Neural Netw Learn Syst 2021 Jun 14;PP. Epub 2021 Jun 14.

The human brain has evolved to perform complex and computationally expensive cognitive tasks, such as audio-visual perception and object detection, with ease. For instance, the brain can recognize speech in different dialects and perform other cognitive tasks, such as attention, memory, and motor control, with just 20 W of power consumption. Taking inspiration from neural systems, we propose a low-power neuromorphic hardware architecture to perform classification on temporal data at the edge. Read More

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Homeostatic and pathogenic roles of the GM3 ganglioside.

FEBS J 2021 Jun 14. Epub 2021 Jun 14.

Core for Medicine and Science Collaborative Research and Education (MS-CORE), Project Research Center for Fundamental Sciences, Osaka University, Osaka, Japan.

Two decades ago, we achieved molecular cloning of ganglioside GM3 synthase (GM3S; ST3GAL5), the enzyme responsible for initiating biosynthesis of complex gangliosides. The efforts of our research group since then have been focused on clarifying the physiological and pathological roles of gangliosides, particularly GM3. This review summarizes our long-term studies on the roles of GM3 in insulin resistance and adipogenesis in adipose tissues, cholesterol uptake in intestine, and leptin resistance in hypothalamus. Read More

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Chemoenzymatic synthesis of complex N-glycans of the parasite S.mansoni to examine the importance of epitope presentation on DC-SIGN recognition.

Angew Chem Int Ed Engl 2021 Jun 14. Epub 2021 Jun 14.

University of Georgia, Complex Carbohydrate Research Center and Department of Chemistry, 315 Riverbend Road, 30602, Athens, UNITED STATES.

The importance of multivalency  for  N -glycan-protein interactions  has primarily been studied by attachment of minimal epitopes to artificial multivalent scaffold and not in the context of multi-antennary glycans.  N -glycans can be modified by bisecting GlcNAc, core xylosides  and fucosides, and extended  N -acetyl lactosamine moieties. The impact of such modifications on glycan recognition are also not well understood. Read More

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An Overview of the Posttranslational Modifications and Related Molecular Mechanisms in Diabetic Nephropathy.

Front Cell Dev Biol 2021 28;9:630401. Epub 2021 May 28.

Department of Chinese Materia Medica and Natural Medicines, School of Pharmacy, The Air Force Medical University, Xi'an, China.

Diabetic nephropathy (DN), a common diabetic microvascular complication, is characterized by its complex pathogenesis, higher risk of mortality, and the lack of effective diagnosis and treatment methods. Many studies focus on the diagnosis and treatment of diabetes mellitus (DM) and have reported that the pathophysiology of DN is very complex, involving many molecules and abnormal cellular activities. Given the respective pivotal roles of NF-κB, Nrf2, and TGF-β in inflammation, oxidative stress, and fibrosis during DN, we first review the effect of posttranslational modifications on these vital molecules in DN. Read More

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Retracted Article: Divergent synthesis of 5-substituted pyrimidine 2'-deoxynucleosides and their incorporation into oligodeoxynucleotides for the survey of uracil DNA glycosylases.

Chem Sci 2020 Oct 7;11(43):11818-11826. Epub 2020 Oct 7.

Department of Medicinal Chemistry, Virginia Commonwealth University Richmond VA 23219 USA +1-804-828-7405.

Recent studies have indicated that 5-methylcytosine (5mC) residues in DNA can be oxidized and potentially deaminated to the corresponding thymine analogs. Some of these oxidative DNA damages have been implicated as new epigenetic markers that could have profound influences on chromatin function as well as disease pathology. In response to oxidative damage, the cells have a complex network of repair systems that recognize, remove and rebuild the lesions. Read More

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October 2020

Cancer Biomarkers Discovery of Methylation Modification With Direct High-Throughput Nanopore Sequencing.

Front Genet 2021 26;12:672804. Epub 2021 May 26.

Center for Molecular Pathology, Department of Basic Medicine, Gannan Medical University, Ganzhou, China.

Cancer is a complex disease, driven by a combination of genetic and epigenetic alterations. DNA and RNA methylation modifications are the most common epigenetic events that play critical roles in cancer development and progression. Bisulfite converted sequencing is a widely used technique to detect base modifications in DNA methylation, but its main drawbacks lie in DNA degradation, lack of specificity, or short reads with low sequence diversity. Read More

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Novel insights for the role of nitric oxide in placental vascular function during and beyond pregnancy.

J Cell Physiol 2021 Jun 14. Epub 2021 Jun 14.

Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile.

More than 30 years have passed since endothelial nitric oxide synthesis was described using the umbilical artery and vein endothelium. That seminal report set the cornerstone for unveiling the molecular aspects of endothelial function. In parallel, the understanding of placental physiology has gained growing interest, due to its crucial role in intrauterine development, with considerable long-term health consequences. Read More

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Beta-klotho in type 2 diabetes mellitus: From pathophysiology to therapeutic strategies.

Rev Endocr Metab Disord 2021 Jun 13. Epub 2021 Jun 13.

Key Laboratory of Glucolipid Metabolic Diseases of The Ministry of Education, Guangzhou, China.

Type 2 diabetes mellitus (T2DM) has become a global health problem with no cure. Despite lifestyle modifications and various pharmaceutical options, the achievement of stable and durable glucose control along with effective prevention of T2DM-related cardiovascular complications remains a challenging task in clinical management. With its selective high abundance in metabolic tissues (adipose tissue, liver, and pancreas), β-Klotho is the essential component of fibroblast growth factor (FGF) receptor complexes. Read More

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Research advances on epigenetics and cancer metabolism.

Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Feb;50(1):1-16

School of Medicine,Tsinghua University,Beijing 100084,China.

Epigenetics concerns gene regulatory mechanisms beyond DNA sequence,such as DNA methylation,histone modification,chromatin remodeling,and non-coding RNA. Epigenetic mechanisms play a key role in development,cell fate decision and tumorigenesis. Chromatin modifications and its high order structure across our genome are major forms of epigenetic information,and its establishment and maintenance are closely related to cell metabolism. Read More

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February 2021

VE-cadherin N-glycosylation modified by GnT-V regulates VE-cadherin/β-catenin interaction and monocyte adhesion.

Exp Physiol 2021 Jun 12. Epub 2021 Jun 12.

College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China.

New Findings: What is the central question of this study? Inflammation-induced monocyte adhesion is the initiator of most vascular diseases. The underlying mechanisms mediating monocyte adhesion remain to be fully clarified. What is the main finding and its importance? GnT-V medicated N-glycosylation on VE-cadherin regulates the dissociation of VE-cadherin/β-catenin complex to modulate the monocyte adhesion, but GnT-V overexpression can not rescue monocyte adhesion induced by IL-1β. Read More

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The Effects of Additional Local-Mixing Compartments in the DISST Model-Based Assessment of Insulin Sensitivity.

J Diabetes Sci Technol 2021 Jun 11:19322968211021602. Epub 2021 Jun 11.

Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand.

Background: The identification of insulin sensitivity in glycemic modelling can be heavily obstructed by the presence of outlying data or unmodelled effects. The effect of data indicative of local mixing is especially problematic with models assuming rapid mixing of compartments. Methods such as manual removal of data and outlier detection methods have been used to improve parameter ID in these cases, but modelling data with more compartments is another potential approach. Read More

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Antibiotic-Impregnated Liquid-Infused Coatings Suppress the Formation of Methicillin-Resistant Biofilms.

ACS Appl Mater Interfaces 2021 Jun 11. Epub 2021 Jun 11.

Department of Surgery, Juravinski Hospital, 711 Concession Street, Hamilton, ON L8V 1C3, Canada.

Medical device-associated infections are an ongoing problem. Once an implant is infected, bacteria create a complex community on the surface known as a biofilm, protecting the bacterial cells against antibiotics and the immune system. To prevent biofilm formation, several coatings have been engineered to hinder bacterial adhesion or viability. Read More

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Synthesis and Antibacterial Activity of Propylamycin Derivatives Functionalized at the 5''- and Other Positions with a View to Overcoming Resistance Due to Aminoglycoside Modifying Enzymes.

ACS Infect Dis 2021 Jun 11. Epub 2021 Jun 11.

Department of Pharmaceutical and Biomedical Sciences, University of Georgia, 250 West Green Street, Athens, Georgia 30602, United States.

Propylamycin (4'-deoxy-4'-propylparomomycin) is a next generation aminoglycoside antibiotic that displays increased antibacterial potency over the parent, coupled with reduced susceptibility to resistance determinants and reduced ototoxicity in the guinea pig model. Propylamycin nevertheless is inactivated by APH(3')-Ia, a specific aminoglycoside phosphotransferase isozyme that acts on the primary hydroxy group of the ribofuranosyl moiety (at the 5''-position). To overcome this problem, we have prepared and studied the antibacterial and antiribosomal activity of various propylamycin derivatives carrying amino or substituted amino groups at the 5''-position in place of the vulnerable hydroxy group. Read More

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Computing with many spaces: Generalizing projections for the digital geohumanities and GIScience.

Proc 1st ACM SIGSPATIAL Workshop Geospat Humanit (2017) 2017 Nov 7;2017:31-38. Epub 2017 Nov 7.

University of California, Berkeley, Berkeley, California.

The digital geohumanities-and geographic computation generally-have advanced greatly by representing phenomena within geographic coordinate systems. More specifically, most visualizations and analyses only proceed once data are rendered into a single coordinate system via geolocation and one or more projections. But does it follow that geographic computation should require all phenomena to be represented in Euclidean or spherical geometry in a singular, absolute, Newtonian space? We suggest an approach to pluralizing available to geographic computation. Read More

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November 2017